11 [0.02-0.19];

=0.01) and in patients with cardiac (coefficient 0.12 [0.02-0.21];

=0.02), and renal diseases (coefficient 0.23 (0.06-0.39);

=0.01). Cardiac disease was the only factor associated with the composite outcome (odds ratio 2.25 [1.19-4.24];

=0.01).

Our results suggest simBTKA is a safe procedure with a low complication rate. However, male patients and those with cardiac and renal diseases are at increased risk of post-operative complications and prolonged hospital stay.

Our results suggest simBTKA is a safe procedure with a low complication rate. However, male patients and those with cardiac and renal diseases are at increased risk of post-operative complications and prolonged hospital stay.

To evaluate the impact of coordination of care of lung cancer in a tertiary care center.

A retrospective study was carried out on all patients diagnosed with lung cancer between 2016-2017 at King Abdulaziz Medical City, Riyadh, Saudi Arabia. Data were collected from medical records, which included demographic data, the interval between cancer suspicion and definitive therapy, multidisciplinary tumor board (MTB) data, and palliative care.

A total of 60 (41 males and 19 females) cases of lung cancer were analyzed. The majority of patients had adenocarcinoma (63.3%) and stage IV (70%) lung cancer. A total of 32 (76.2%) of stage IV patients were referred to palliative care. Only 40 (66.7%) of the patients were presented in the MTB, of whom new findings were found in 15 (37.5%) patients including pathology findings in 3 (7.5%), radiology findings in 7 (17.5%), and staging data in 5 (12.5%). Multidisciplinary tumor board discussion had impacted the management in 14 (35%) of patients presented.

Discussion of lung cancer cases in MTB had a positive influence on the coordination of patients’ care.

Discussion of lung cancer cases in MTB had a positive influence on the coordination of patients’ care.An outbreak of novel coronavirus disease-2019 (COVID-19) was reported in Wuhan, China, in December 2019, which was later declared a global pandemic by the World Health Organization (WHO) in March 2020. It is a life-threatening contagious infection with infected patients usually presenting with respiratory tract symptoms, although the disease can affect other multiple organs. Coronavirus disease-2019 infection is a hypercoagulable state associated with serious thrombotic complications, particularly in critically ill patients. However, these thrombotic complications are also being reported as a presenting symptom in asymptomatic and mildly symptomatic cases of COVID-19 infection in the absence of any other predisposing risk factors. Renal infarction is one of these thrombotic complications and can present with ambiguous abdominal symptoms leading to irreversible organ damage and other thromboembolic complications, if not diagnosed in time. Physicians must be aware of such uncommon presenting complaints of COVID-19 infection and include it in the differential diagnosis of patients presenting with abdominal symptoms.

To generate a translated Arabic adaptation of the revised Moorehead-Ardelt Quality of Life Questionnaire II (MA-II), then to assess its reliability and validity.

The MA-II was translated to Arabic by 3 independent translators. Next, a concise translation, developed from the 3 translations, was re-translated to English and was compared with the original questionnaire. Both the reliability and the validity of the Arabic MA-II were assessed in 144 patients struggling with obesity before and after bariatric procedures at Khalid University Hospital, Riyadh, Saudi Arabia. Apart from the demographic data, both the MA-II and the 36-item short-form health survey (SF-36) were used to collect health-related quality of life (HRQL) data. The test-retest method and Cronbach’s alpha (α)were used to assess reliability and internal consistency.

Test-retest reliability exhibited an intraclass correlation coefficient of 0.966. The internal consistency of the translated version was also high (α=0.812). A satisfactory correlation was demonstrated between the translated Arabic version and the 8 items of the SF-36. A significant negative correlation was also observed between the MA-II and body mass index (r= -0.5778,

<0.001).

The robustness and sustainability of the translated Arabic version of the MA-II suggested that this disease-specific instrument is a reliable and valid tool for the measurement of HRQL in obease Arabic-speaking people.

The robustness and sustainability of the translated Arabic version of the MA-II suggested that this disease-specific instrument is a reliable and valid tool for the measurement of HRQL in obease Arabic-speaking people.

To measure the self-awareness of hemoglobin A1c (HbA1c) prevalence among type 2 diabetic Saudi patients and its association with glycemic control, thereby identifying those factors that might affect their glycemic control.

This multicenter study was carried out in outpatients’ diabetes clinics in tertiary hospitals in Riyadh, Qassim, and Jeddah, Saudi Arabia. The data was collected using questionnaires. The subject’s self-awareness on the HbA1c test was assessed based on the combined score of 4 questions. The latest HbA1c result before the time of data collection was obtained from medical records. Data was analyzed using bivariate and multivariate statistical methods.

The prevalence of HbA1c self-awareness was approximately 44.5%. A total of 4 participants characteristics (glycemic control, education level, monthly income and number of follow-up visits) were associated with awareness of HbA1c. Whereas for better glycemic control; type of treatment, duration of diabetes, and self-awareness of HbA1c were to study this association, which will contribute to the development of a structured educational program.

To describe the frequency and spectrum of different types of gynecological malignancies (malignant tumors of the female genital tract) and to characterize the pattern of gynecological neoplasms in different age groups in Al-Madinah Al-Munawarah, Saudi Arabia.

This 6-year retrospective-design research was carried out on different age groups in Al-Madinah Al-Munawarah region, from June 2015 until June 2021. The patients’ information of all 200 specimens, including age, nationality, tumor site, and pathological disorders was obtained from the Maternity and Children Hospital, Al-Madinah Al-Munawarah.

Endometrial cancer was the most common malignancy for women of 31 years and above (69.0%). Tumors of the uterine corpus were mostly epithelial (86.7%) and possessed an endometrioid carcinoma histology (90.6%). There was only a small decline in gynecological cancer incidences in Al-Madinah Al-Munawarah over the past 6 years.

Most of the cancer incidences, regardless of the pathological diagnosis, either increased or remained unchanged over time, is a possible indication of the current state of health programs and information available to the citizens in Al-Madinah Al-Munawarah. Further studies exploring the economic background of diagnosed patients may be of interest to future research.

Most of the cancer incidences, regardless of the pathological diagnosis, either increased or remained unchanged over time, is a possible indication of the current state of health programs and information available to the citizens in Al-Madinah Al-Munawarah. Further studies exploring the economic background of diagnosed patients may be of interest to future research.

To investigate the rate of laryngospasm with sedation during the esophagogastroduodenoscopy (EGD) procedure in children exposed to passive smoking and to examine the frequency of complications due to laryngospasm.

A single-blind, prospective, observational study with a total of 518 patients evaluated according to the American Society of Anesthesiologists (ASA) physical status as classification I-II, aged between 1-18 years, and planned to undergo an EGD procedure, were included. Age, gender, weight, ASA assessment, exposure to smoking (the mother, the father, both parents were smokers, or not exposed to smoking), drug doses used in sedation, and anesthesia-related complications, such as cough, decrease in oxygen saturation, and laryngospasm were recorded.

Of the 518 patients included in the study, 213 had no smoking exposure history. Oxygen saturation did not decrease below 90% in patients who did not have any smoking exposure. In addition, no laryngospasm was observed in this group. However, 4 (11.4%) of 31 patients whose mother only smoked, 10 (5.1%) of 187 child patients whose father only smoked, and 12 (16.4%) of 61 patients whose mother and father both smoked experienced laryngospasm during the procedure.

The rate of cough, laryngospasm, and hypoxia development increased during the sedation carried out in the EGD procedure in children who were exposed to passive smoke.

.

The rate of cough, laryngospasm, and hypoxia development increased during the sedation carried out in the EGD procedure in children who were exposed to passive smoke.Clinicaltrial.gov ID NCT03920046.

To assess the otorhinolaryngological (ORL) symptoms, including their prevalence, severity, and early presentations among coronavirus disease-19 (COVID-19) patients in the Saudi population.

This was a multicentric, cross-sectional study carried out on severe acute respiratory syndrome coronavirus-2 positive patients at 3 COVID-19 centres; Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, ALKhobar, Qatif Central Hospital, AlQatif, and Ohud Hospital, Al Madinah Al Munawarah, Saudi Arabia. The validated survey consisted of sociodemographic data, general symptoms of COVID-19, and ORL manifestations.

A total of 1734 COVID-19 positive patients were included in the study (mean age 37.7±11.6 years). Most of the cases were mild (51.8%), followed by moderate (45.6%), and severe (2.6%) cases. Approximately 33.7% were asymptomatic. Severity of symptoms was significantly associated with male gender (

=0.017), higher age-group (

=0.04), and smoking (

<0.001). The most common initial ORL presentations were sore throat (20.9%), anosmia (15.5%), hyposmia (10%), and loss of taste (11.4%). Overall, 79.5% showed ORL symptoms as the initial presenting symptoms for COVID-19, with anosmia and sore throat being the most common symptoms.

This study confirmed the prevalence of ORL symptoms among COVID-19 patients in Saudi Arabia. Moreover, these symptoms could also be considered for early detection of COVID-19 as they might appear prior to other symptoms.

This study confirmed the prevalence of ORL symptoms among COVID-19 patients in Saudi Arabia. Moreover, these symptoms could also be considered for early detection of COVID-19 as they might appear prior to other symptoms.

To determine the influence of coronavirus disease-19 (COVID-19) on cochlear tasks of children who had COVID-19 previously, and the relevance among disease seriousness and cochlear involvement by otoacoustic emissions (OAEs).

The study included 24 hospitalized children after COVID-19 diagnosis, 23 pediatrics that received outpatient treatment, and 21 children who were without COVID-19 diagnosis as the control group between June 2021 and July 2021. Transient evoked otoacoustic emission (TEOAE), distortion product otoacoustic emission, and contrlateral suppression of otoacoustic emission measurements were carried out for each child. Symptoms of patients, the treatments they received, and the duration of hospitalization of the children in the hospitalized group were recorded.

The comparison of TEOAE test results under masking showed a considerable difference between 3 groups at 1 kHz (

=0.033) and 4 kHz (

=0.021) frequencies (

<0.05). Distortion product otoacoustic emission test results of hospitalized outpatient and control group showed a statistically significant difference at 2 kHz among themselves (

=0.009).

Our results suggest that severe acute respiratory syndrome coronavirus-2 may influence the medial olivocochlear system of children and have irreversible effects on the cochlear functions. Early detection of problems that may affect cochlear functions is a special critical task, especially in children, who are a particularly vulnerable group in terms of hearing and related speech problems.

Our results suggest that severe acute respiratory syndrome coronavirus-2 may influence the medial olivocochlear system of children and have irreversible effects on the cochlear functions. Early detection of problems that may affect cochlear functions is a special critical task, especially in children, who are a particularly vulnerable group in terms of hearing and related speech problems.

To determine the risk factors associated with mortality in premature newborns (PNB).

An observational, descriptive, and retrospective study, carried out at the General Hospital of San Juan del Rio, Queretaro, Mexico. The medical records of PNB admitted to the Neonatal Intensive Care Unit from January until December 2018 were studied.

A total of 136 PNB were included (74 males and 62 females) of whom 16 (11.7%) died (9 males and 7 females). A correlation was observed between gestational age and birth weight with Apgar values at 1 and 5 minutes (r=0.37,

<0.001). A lower birth weight was found in premature infants with infectious diseases, as well as a lower gestational age in relation to respiratory diseases (

<0.0001). The PNB with Apgar values lower than 7 points at 1 and 5 minutes were more likely to die (

<0.0001). The PNB with very low birth weight (1-1.49 kg), with less than 28 weeks of gestation, and with infectious pathology showed more probabilities of dying (

<0.05).

Apgar values lower than 7 points in the PNB are associated with the presence of infectious diseases and mortality. Likewise, a lower gestational age represents a lower birth weight, with a higher risk for respiratory and infectious diseases, and consequently an elevated mortality.

Apgar values lower than 7 points in the PNB are associated with the presence of infectious diseases and mortality. Likewise, a lower gestational age represents a lower birth weight, with a higher risk for respiratory and infectious diseases, and consequently an elevated mortality.

To establish the frequency of Dombrock (DO) blood group genotypes in Western Saudi Arabians and to compare the findings with other populations in the 1000 genomes database.

This cross-sectional study was carried out between December 2018 and February 2019. A total of 440 blood samples in ethylenediaminetetraacetic acid tubes were collected from unrelated Saudi Arabian blood donors from Jeddah, Saudi Arabia. Deoxyribonucleic acid was extracted, followed by an allele-specific polymerase chain reaction for DO*01 and DO*02 alleles (

,

). The allele and genotype frequencies were counted and compared to those in other populations using the Chi-squared test with Bonferroni adjustments.

The DO allele frequencies for blood donors from western Saudi Arabia were 0.432 for DO*01 and 0.568 for DO*02. The DO genotype frequencies were 0.182 for DO*01/01, 0.318 for DO*02/02, and 0.5 for DO*01/02. The DO genotype frequencies were similar to Europeans, Americans, and South Asians but significantly different from the genotype frequencies of Africans and East Asians reported in the 1000 genomes database.

Dombrock genotype frequencies in the Western Saudi Arabian population were different from Africans and East Asians but not from Europeans, Americans, and South Asians. This study contributes to a genotyped blood donor database and may advance transfusion safety for patients in western Saudi Arabia.

Dombrock genotype frequencies in the Western Saudi Arabian population were different from Africans and East Asians but not from Europeans, Americans, and South Asians. This study contributes to a genotyped blood donor database and may advance transfusion safety for patients in western Saudi Arabia.

To identify the carbapenemase producing Gram-negative bacteria (GNB) by phenotypic methods and to confirm the presence of resistant genes using real-time polymerase chain reaction (PCR).

This was a prospective study carried out at the Department of Microbiology, Sri Venkata Sai Medical College and Hospital, Mahabubnagar, India, from March 2018-2021. All samples were screened for carbapenem resistance by disc diffusion method and the VITEK

2 compact system (bioMérieux, France). Detection of carbapenemase was carried out using RAPIDEC

CARBA NP test (Biomeriux Private Limited, South Delhi, India), screening for metallo-β-lactamases (MBL) was carried out by double disk synergy test (DDST), and genotypic characterization by real-time PCR.

Among the 1093 Gram-negative bacilli identified, 220 (17.0%) were resistant to carbapenems by both tested methods. Carbapenemase detection using the RAPIDEC

CARBA NP test indicated that 207 (94.0%) were carbapenemase producers, of which 189 (91.2%) were MBL producers. The most common carbapenemase genes identified were New Delhi metallo-β-lactamase (NDM; 47.3%), followed by the co-existence of genes in combination of NDM, with Verona integron-mediated metallo-β-lactamase (VIM; 39.6%), VIM and oxacillin hydrolyzing enzymes-48 (OXA-48; 4.3%), and OXA-48 (1.4%).No gene of active on imipenem,

carbapenemase, VIM, or OXA-48 alone was detected.

This study suggests routine carbapenem resistance testing among multi-drug resistant-GNBs, as most of these infections occur in hospitals. In addition, there is a possibility that these highly antibiotic-resistant genes could spread to other bacteria resulting in further dissemination.

This study suggests routine carbapenem resistance testing among multi-drug resistant-GNBs, as most of these infections occur in hospitals. In addition, there is a possibility that these highly antibiotic-resistant genes could spread to other bacteria resulting in further dissemination.

To assess the impact of low-flow, mid-flow, and high-flow sevoflurane anesthesia on the oxidative state by measuring thiol/disulfide levels in patients undergoing surgery.

The study included 99 patients randomly assigned to 3 groups. In the low-flow anesthesia group, the fresh gas flow was diminished to 1 L.min

for anesthesia maintenance after 6 L.min

was administered for the first 10 minutes. In the mid-flow anesthesia group, fresh gas flow was applied as 2 L.min

. In the high-flow anesthesia group, the fresh gas flow was administered as 4 L.min

throughout the operation. Blood samples were obtained before induction, at the 60th minute after induction, and at 2 hours postoperatively. Native thiol, total thiol, disulfide analyzed and disulfide/native thiol percentage, disulfide/total thiol percentage, and native thiol/total thiol percentage were calculated.

Disulfide values in mid-flow and low-flow anesthesia were significantly lower at the 60th minute after induction compared to the high-flow anesthesia group. In the group evaluations, intraoperative native thiol levels in the high-flow group were found to be substantialy lower than preoperative values.

It was sighted that low-flow anesthesia with sevoflurane prohibited oxidative damage. It was concluded that low flow anesthesia can be utilized safely in this respect.

It was sighted that low-flow anesthesia with sevoflurane prohibited oxidative damage. It was concluded that low flow anesthesia can be utilized safely in this respect.COVID-19 vaccine requirements have generated significant debate. Here, we argue that, on the evidence available, such policies should have recognised proof of natural immunity as a sufficient basis for exemption to vaccination requirements. We begin by distinguishing our argument from two implausible claims about natural immunity (1) natural immunity is superior to 'artificial’ vaccine-induced immunity simply because it is 'natural’ and (2) it is better to acquire immunity through natural infection than via vaccination. We then briefly survey the evidence base for the comparison between naturally acquired immunity and vaccine-induced immunity. While we clearly cannot settle the scientific debates on this point, we suggest that we lack clear and convincing scientific evidence that vaccine-induced immunity has a significantly higher protective effect than natural immunity. Since vaccine requirements represent a substantial infringement of individual liberty, as well as imposing other significant costs, they can only be justified if they are necessary for achieving a proportionate public health benefit. Without compelling evidence for the superiority of vaccine-induced immunity, it cannot be deemed necessary to require vaccination for those with natural immunity. Subjecting them to vaccine mandates is therefore not justified. We conclude by defending the standard of proof that this argument from necessity invokes, and address other pragmatic and practical considerations that may speak against natural immunity exemptions.

FOCUS4 was a phase II/III umbrella trial, recruiting patients with advanced or metastatic colorectal cancer, between 2014 and 2020. Molecular profiling of patients’ formalin-fixed, paraffin-embedded tumour blocks was undertaken at two centralised biomarker laboratories (Leeds and Cardiff), and the results fed directly to the Medical Research Council Clinical Trials Unit, and used for subsequent randomisation. Here the laboratories discuss their experiences.

Following successful tumour content assessment, blocks were sectioned for DNA extraction and immunohistochemistry (IHC). Pyrosequencing was initially used to determine tumour mutation status (KRAS, NRAS, BRAF and PIK3CA), then from 2018 onwards, next-generation sequencing was employed to allow the inclusion of TP53. Protein expression of MLH1, MSH2, MSH6, PMS2 and pTEN was determined by IHC. An interlaboratory comparison programme was initiated, allowing sample exchanges, to ensure continued assay robustness.

1291 tumour samples were successfully anaNational Health Service mutation analysis services were challenging. The laboratories benefitted from both pretrial validations and interlaboratory comparisons, resulting in robust assay development and provided confidence during the implementation of new sequencing technologies. We conclude that our centralised approach to biomarker testing in FOCUS4 was effective and successful.

The identification of possible hippocampal alterations is a crucial point for the diagnosis and therapy of patients with unilateral temporal lobe epilepsy (TLE). This study aims to investigate the role of neurite orientation dispersion and density imaging (NODDI) compared to diffusion tensor imaging (DTI) in the comprehension of hippocampal microstructure in TLE.

DTI and NODDI metrics were calculated in the hippocampi of adult patients with TLE, with and without histology-confirmed hippocampal sclerosis (HS), and in age/sex-matched healthy controls (HC). Diffusion metrics and hippocampal volumes of the pathologic side were compared within participants and between participants among the HS, non-HS, and HC groups. Diffusion metrics were also correlated with hippocampal volume and patients’ clinical features. After surgery, hippocampal specimens were processed for neuropathology examinations.

Fifteen patients with TLE (9 with and 6 without HS) and 11 HC were included. Hippocampal analyses resulted in a sigi positively correlated with disease duration (

= 0.684,

= 0.0424 and

= 0.670,

= 0.0486, respectively). Immunohistochemistry in sclerotic hippocampal specimens revealed neuronal loss in the pyramidal layer and fiber reorganization at the level of stratum lacunosum-moleculare, confirming ODI and ND metrics.

This study shows the capability of diffusion MRI metrics to detect hippocampal microstructural alterations. Among them, ODI seems to better highlight the fiber reorganization observed by neuropathology in sclerotic hippocampi.

This study shows the capability of diffusion MRI metrics to detect hippocampal microstructural alterations. Among them, ODI seems to better highlight the fiber reorganization observed by neuropathology in sclerotic hippocampi.

I-meta-iodobenzyl-guanidine (

I-MIBG) myocardial scintigraphy is used as a diagnostic imaging test to differentiate Lewy body diseases (LBDs), including Parkinson disease and dementia with Lewy bodies, from other similar diseases. However, this imaging test lacks validation of its diagnostic accuracy against the gold standard. Our aim was to validate the diagnostic accuracy of

I-MIBG myocardial scintigraphy for LBD against autopsy, the gold standard.

This retrospective, cross-sectional study included consecutive autopsy patients from the Brain Bank for Aging Research who had undergone

I-MIBG myocardial scintigraphy. We compared the

I-MIBG myocardial scintigraphy findings with autopsy findings. Furthermore, the proportion of residual tyrosine hydroxylase (TH)-immunoreactive sympathetic fibers in the anterior wall of the left ventricle was investigated to assess the condition of the cardiac sympathetic nerves assumed to cause reduced

I-MIBG uptake in LBDs.

We analyzed the data of 56 patients (30 iac sympathetic denervation. However, LBD pathology should not necessarily be excluded by normal myocardial scintigraphy results, especially when other biomarkers suggest the presence of comorbid Alzheimer disease pathology.

This study provides Class II evidence that

I-MIBG myocardial scintigraphy accurately identifies patients with LBD.

This study provides Class II evidence that 123I-MIBG myocardial scintigraphy accurately identifies patients with LBD.Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant embryonal tumor of the CNS, largely affecting pediatric patients, with exceedingly rare cases in adults at an estimated annual incidence of 1/1,000,000. We report a unique case of ATRT in a 43-year-old female patient who first presented with progressive focal headaches. Imaging revealed a sellar mass with suprasellar extensions, which was partially removed via a transsphenoidal resection. The tumor aggressively recurred just 1 month postoperatively. Her care team pursued a novel treatment plan by using a slightly modified COG ACNS 0332 regimen, which involved radiation, followed by 4 cycles of monthly chemotherapy including vincristine, cyclophosphamide, and cisplatin. Hematopoietic stem cells were collected between radiation and chemotherapy in the event that the patient required stem cell salvage therapy postadjuvant chemotherapy. The MRIs taken at 2 and 4 months postrecurrence indicated a substantial decrease in tumor volume, with corresponding clinical improvements to cranial nerve deficits. Given the scarcity of literature on adult cases of ATRT and the lack of a standard of care for these cases, discussing the efficacy of our patient’s treatment plan may aid clinical decision making for adult ATRT cases.

Although patients hospitalized with COVID-19 frequently present with encephalopathy, those with mild initial COVID-19 disease who never required hospitalization also often develop neurologic symptoms as part of postacute sequelae of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection (neuro-PASC). The pathogenic mechanisms of COVID-19 encephalopathy and neuro-PASC are unknown. We sought to establish biochemical evidence of CNS injury in those patients and their association with neuropsychiatric manifestations and SARS-CoV-2 antigenemia.

We recruited hospitalized, posthospitalized, and nonhospitalized patients with confirmed diagnosis of COVID-19 with neurologic symptoms in addition to healthy control (HC) subjects. Plasma neurofilament light chain (pNfL), plasma glial fibrillary acidic protein (pGFAP), and plasma SARS-CoV-2 Nucleocapsid antigen (pN Ag) were measured by HD-X Simoa analyzer (Quanterix) and compared with neuropsychiatric symptoms, patient-reported quality-of-life measures, andencephalopathy. Detection of SARS-CoV-2 N Ag in blood 3 weeks after symptoms onset in a nonhospitalized patient suggests that prolonged antigenic stimulation, or possibly latent infection, may occur. Anxiety was associated with evidence of astroglial activation in patients with neuro-PASC. These data shed new light on SARS-Cov-2 neuropathogenesis and demonstrate the value of plasma biomarkers across the COVID-19 disease spectrum.

pNfL, pGFAP, and pN Ag measurements indicate neuronal dysfunction and systemic involvement in hospitalized COVID-19 patients with encephalopathy. Detection of SARS-CoV-2 N Ag in blood 3 weeks after symptoms onset in a nonhospitalized patient suggests that prolonged antigenic stimulation, or possibly latent infection, may occur. Anxiety was associated with evidence of astroglial activation in patients with neuro-PASC. These data shed new light on SARS-Cov-2 neuropathogenesis and demonstrate the value of plasma biomarkers across the COVID-19 disease spectrum.Although recognized as a curable disease, the persistence of hepatitis C virus (HCV) in chronically infected patients remains a great burden for public health. T cell immune responses serve a key role in anti-HCV infection; however, the features of T cell immunity in patients after a long-term infection are not well explored. We recruited a special cohort of patients with similar genetic background and natural developing progression of disease who were infected with HCV through blood donation 35 y ago. We found that self-resolved individuals had higher levels of cytokine-secreting T cells than individuals with chronic infections, indicating HCV-specific T cell immunity could be sustained for >35 y. Meanwhile, virus-specific CD8+ T cells in chronic patients were characterized by programmed cell death-1high, TIM-3high expression, which was related to liver injury characterized by aspartate transaminase/alanine aminotransferase levels and morphopathological changes. Unexpectedly, the expression of Lymphocyte-activation gene 3 on CD8+ T cells was lower in chronic patients and negatively correlated with alanine aminotransferase/aspartate transaminase. Our findings provided new insights into HCV-specific T cell responses and may shed light on a way to figure out novel effector targets and explore a way to reverse chronic infections.BACKGROUND Neonatal abstinence syndrome (NAS) is a complex disorder characterized by withdrawal symptoms secondary to in utero exposure to drugs capable of producing physical dependence. The objective of this study was to determine the incidence of NAS, as well as infant and maternal characteristics associated with NAS in North Carolina (NC).METHODS This retrospective, cross-sectional, observational study used the State Inpatient Database (SID) to compare the incidence rates of NAS for NC for the year 2016 to historical data (years 2000 to 2013). A multivariable logistic regression model including available covariates of interest was constructed.RESULTS Overall NAS incidence rate (IR) for NC was found to be 9.7 per 1,000 live births, a 32.3-fold increase since 2000 (IR=0.3 in 2000). The multivariable logistic regression model suggested race group (both black [OR 0.11; 95% CI 0.08, 0.16] and 'other’ [OR 0.43; 95% CI 0.31, 0.61] vs white), ethnicity [OR 0.43; 95% CI 0.31, 0.61], insurance group (both 'other/self-pay’ [OR 0.35; 95% CI 0.24, 0.52] and 'private insurance’ [OR 0.07; 95% CI 0.05, 0.10] vs Medicaid/Medicare), region (Piedmont [OR 0.62; 95% CI 0.50, 0.79] vs Mountain), income quartile (both 4th [OR 0.45; 95% CI 0.26, 0.79] and 3rd [OR 0.70; 95% CI 0.50, 0.96] vs 1st), county population size (50k-249k [OR 0.54; 95% CI 0.34, 0.86] vs ≥1 million), birth weight [OR 0.87; 95% CI 0.78, 0.98], and length of stay [OR 1.23; 95% CI 1.20, 1.26] as potentially important predictors of NAS.LIMITATIONS Only hospitals providing data to the SID for 2016 were included and ICD-9 codes, in use at the time of data collection, were used.CONCLUSIONS The incidence of NAS has increased in NC in 2016 compared to prior years spanning back to 2000. Specific infant and maternal characteristics including race, ethnicity, payer type, geographic region, county population, parental income status, birth weight, and length appear to be associated with an infant bearing the diagnosis of NAS.BACKGROUND Cardiac rehabilitation (CR) can improve quality of life and reduce subsequent hospitalizations for individuals with cardiovascular disease. Nevertheless, CR is underutilized, and less is known about the current content, patient population, and workforce of CR programs in North Carolina.OBJECTIVE To describe CR services, patient participation, and workforce in North Carolina in order to characterize CR infrastructure and identify opportunities to improve CR use.METHODS We distributed an electronic survey to all certified outpatient CR programs in North Carolina in spring 2019. Descriptive statistics were used to summarize program characteristics, participant characteristics, and current workforce. Data were analyzed overall and by region.RESULTS Responding programs (89.5% response rate, n=68) had been in operation for a mean of 24 (SD 10.4) years. Programs have similar availability across the state, operating 4 days a week with 5 sessions per day. A majority of programs offered nutrition counseling (98.5%), stress management (94.1%), aerobic exercise (86.8%), and weight training (86.8%). Patients were majority male (65%), aged 65 or older (75%), and White (75%). Nearly half of patients referred to CR attended at least 1 session, though 25% discontinued early. Most programs were staffed by a median of 2 full-time nurses (97%) and by a median of 1.5 full-time exercise physiologists (96%). Mental health and administrative professionals were less frequent in CR settings.LIMITATIONS Since this survey was primarily completed by program directors, further research is needed to understand the challenges, experiences, and needs of the frontline CR workforce, as well as the direct experiences of patients who participate in CR.CONCLUSIONS CR programs in North Carolina offer a range of services. While half of patients referred to CR initiate services, interventions are needed to improve initiation and adherence to CR.BACKGROUND Rural, primary care providers face particular challenges with adapting the delivery of care in the setting of the Coronavirus Disease of 2019 (COVID-19) pandemic. Project ECHO® is a virtual, case-based platform centered on collective learning. As a regional Area Health Education Center (AHEC), we developed two Project ECHO® series aimed at disseminating best practices and creating a community of shared experiences for rural providers.METHODS On March 30, 2020, we launched two Project ECHO® series pertaining to COVID-19 the Primary Care COVID-19 Collaborative series and the Practice Support for COVID-19 Preparedness series. These series each occurred twice weekly, concluding in February 2021, and were free to attend. Topics include COVID-19-specific management as well as strategies for adapting the delivery of care during the pandemic. We assessed engagement per county as well as attendee evaluations.RESULTS In the first month, we hosted 19 sessions with 283 participants from 37 counties in North Carolina. Providers felt the most impactful aspects of the sessions were the changes to their practice and the lateral learning from peers in the region.LIMITATIONS In review of our survey responses, a small percentage of our participants do not appear to have direct patient care roles, so we believe this impacted our survey results particularly in regard to relevance to clinical practice and change to clinical practice.CONCLUSIONS Project ECHO® is an effective platform for quickly disseminating information and creating a sense of community in the midst of the social distancing required during the pandemic.The following is a review of current policy and proposed legislation related to physical environment indicators in North Carolina. It is not an endorsement of any policy or bill; it is meant to serve as a resource for policy makers, health care stakeholders, and other readers of the NCMJ.Limited access to healthy foods can lead to negative health outcomes such as cardiovascular conditions and diabetes. In North Carolina, there are more than 350 „food deserts” where it is difficult for more than 1.5 million residents to access healthy food. In Watauga County, Blue Ridge Women in Agriculture works to fill that gap.Housing’s impact on health goes beyond the need for a roof over one’s head. Severe housing problems, such as overcrowding, high housing costs, or lack of plumbing or kitchen facilities, contribute to poor health outcomes ranging from asthma to heart disease. Michelle Kennedy, Greensboro’s neighborhood development director, discusses policies to improve housing quality in North Carolina.The social conditions in which people live, including their housing, can have a profound impact on their health. The North Carolina Healthy Opportunities Pilots aim to address housing problems and other social needs to improve health. The results from the Pilots’ evaluation will have important implications for health policy and practice.The physical environment-the places where individuals live, work, and play-can cause or prevent serious health conditions including chronic diseases and obesity. In North Carolina, the Collective Impact Model serves as the foundation on which multisector community coalitions can address environmental and policy barriers for improved health.The urban-rural divide in chronic disease contributes to persistent geographic disparities in life expectancy in North Carolina. Policies and programs in resource-constrained rural areas should be designed to increase health equity and reduce this continuing divide by including greater community engagement and decision-making for meaningful, sustainable change.The built environment is a key social determinant of health. Exposure to parks and greenspace can improve physical and mental health and provide other benefits that enhance well-being. Programs and initiatives that capitalize on nature-based opportunities offer health care providers with a cost-effective alternative for upstream health promotion.Housing costs, eviction rates, homelessness, and the number of families living in substandard conditions are rising quickly. The poor quality of housing and high rates of evictions today will result in additional health issues and challenge systems to meet the „Healthy North Carolina 2030” housing goals.Per- and polyfluoroalkyl substances (PFASs), a family of human-made chemicals often described as „forever chemicals,” are observed in a wide range of products utilized by North Carolinians and can cause liver damage, cancer, and infertility. Owing to their widespread use and persistence in the environment, humans and animals are exposed to individual and combinations of PFASs.The physical environment in which we live, work, and play has everything to do with our overall well-being and health. This issue of the North Carolina Medical Journal focuses on those physical structures, environmental factors, and access issues that impact North Carolinians’ ability to make healthy choices and the policy changes that could improve indicators like access to healthy food, exercise opportunities, and secure and safe housing.

Appendiceal diameter is a primary sonographic determinant of paediatric appendicitis. We sought to determine if the diagnostic performance of outer appendiceal diameter differs based on age or with the addition of secondary sonographic findings.

We retrospectively reviewed patients aged less than 19 years who presented to the Boston Children’s Hospital ED and had an ultrasound (US) for the evaluation of appendicitis between November 2015 and October 2018. Our primary outcome was the presence of appendicitis. We analysed the cases to evaluate the optimal outer appendiceal diameter as a predictor for appendicitis stratified by age (<6, 6 to <11, 11 to <19 years), and with the addition of one or more secondary sonographic findings.

Overall, 945 patients met criteria for inclusion, of which 43.9% had appendicitis. Overall, appendiceal diameter as a continuous measure demonstrated excellent test performance across all age groups (area under the curve (AUC) >0.95) but was most predictive of appendonographic findings increases diagnostic performance.

This study aimed to investigate the clinical characteristics and outcomes of pregnancy complicated by SLE-associated pulmonary arterial hypertension (SLE-PAH) in a case series and literature review.

This single-centre retrospective study included 10 consecutive pregnancies complicated by SLE-PAH confirmed by right heart catheterisation (RHC) at Peking Union Medical College Hospital between 2009 and 2020. A literature search was conducted and 14 pregnancy cases complicated by SLE-PAH were reviewed.

At the time of 10 patients’ initial visits, the average age was 30.00±5.72 years and the median disease duration of SLE and PAH was 34.5 (range 1-164) months and 2 (1-51) months. Two patients carried planned pregnancy, seven patients developed PAH during pregnancy and one pregnancy was unplanned. Further, nine patients had low disease activity, with Systemic Lupus Erythematosus Disease Activity Index between 0 and 4, and 30%, 30% and 40% of patients were of WHO functional class II, III and IV, respectively. Al7 years. The median time of completed pregnancies was 36 (28-40) weeks. More cases were planned and successful, and the survival rates of mothers and neonates were 85.71% and 92.86%, respectively.

Successful pregnancy could be possible in women with SLE-PAH if SLE-PAH treatment goals are achieved under proper therapies, careful monitoring and thorough evaluations.

Successful pregnancy could be possible in women with SLE-PAH if SLE-PAH treatment goals are achieved under proper therapies, careful monitoring and thorough evaluations.Hereditary transthyretin amyloidosis (ATTRv) is a severe, adult-onset autosomal dominant inherited systemic disease predominantly affecting the peripheral and autonomic nervous system, heart, kidney and the eyes. ATTRv is caused by mutations of the transthyretin (TTR) gene, leading to extracellular deposition of amyloid fibrils in multiple organs including the peripheral nervous system. Typically, the neuropathy associated with ATTRv is characterised by a rapidly progressive and disabling sensorimotor axonal neuropathy with early small-fibre involvement. Carpal tunnel syndrome and cardiac dysfunction frequently coexist as part of the ATTRv phenotype. Although awareness of ATTRv polyneuropathy among neurologists has increased, the rate of misdiagnosis remains high, resulting in significant diagnostic delays and accrued disability. A timely and definitive diagnosis is important, given the emergence of effective therapies which have revolutionised the management of transthyretin amyloidosis. TTR protein stabilisers diflunisal and tafamidis can delay the progression of the disease, if treated early in the course. Additionally, TTR gene silencing medications, patisiran and inotersen, have resulted in up to 80% reduction in TTR production, leading to stabilisation or slight improvement of peripheral neuropathy and cardiac dysfunction, as well as improvement in quality of life and functional outcomes. The considerable therapeutic advances have raised additional challenges, including optimisation of diagnostic techniques and management approaches in ATTRv neuropathy. This review highlights the key advances in the diagnostic techniques, current and emerging management strategies, and biomarker development for disease progression in ATTRv.The Human Reference Genome serves as the foundation for modern genomic analyses. However, in its present form, it does not adequately represent the vast genetic diversity of the human population. In this study, we explored the consensus genome as a potential successor of the current reference genome and assessed its effect on the accuracy of RNA-seq read alignment. To find the best haploid genome representation, we constructed consensus genomes at the pan-human, superpopulation, and population levels, using variant information from The 1000 Genomes Project Consortium. Using personal haploid genomes as the ground truth, we compared mapping errors for real RNA-seq reads aligned to the consensus genomes versus the reference genome. For reads overlapping homozygous variants, we found that the mapping error decreased by a factor of approximately two to three when the reference was replaced with the pan-human consensus genome. We also found that using more population-specific consensuses resulted in little to no increase over using the pan-human consensus, suggesting a limit in the utility of incorporating a more specific genomic variation. Replacing the reference with consensus genomes impacts functional analyses, such as differential expressions of isoforms, genes, and splice junctions.Cisplatin-induced ototoxicity can be partially attributed to excessive reactive oxygen species (ROS) production, and agmatine is well-known for the activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway to inhibit ROS production. Whether agmatine could be used to alleviate cisplatin-induced ototoxicity is investigated. Cisplatin-exposed House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear explants showed increased ROS production detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining and decreased cell viability detected by Cell Counting Kit-8 (CCK-8) or Myosin 7a staining, which could be reversed by the agmatine pretreatment. Cisplatin intraperitoneally injected C57BL/6 mice demonstrated damaged auditory function as indicated by distortion products otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) assays, and trans-tympanically administrated agmatine in the left ears could partly prevent the auditory function loss. Mechanistically, downregulated B-cell lymphoma 2 (Bcl-2) expression, upregulated Bcl2-associated x (Bax) expression, and diminished p-PI3K and p-AKT expression were detected in cisplatin-exposed HEI-OC1 cells and cochlear explants, which could be prevented by the pretreatment with agmatine. Our investigation demonstrates that agmatine pretreatment could alleviate cisplatin-induced ototoxicity with the activation of PI3K/AKT signaling pathway.Mitochondria possess their own genome that encodes components of oxidative phosphorylation (OXPHOS) complexes, and mitochondrial ribosomes within the organelle translate the mRNAs expressed from the mitochondrial genome. Given the differential OXPHOS activity observed in diverse cell types, cell growth conditions, and other circumstances, cellular heterogeneity in mitochondrial translation can be expected. Although individual protein products translated in mitochondria have been monitored, the lack of techniques that address the variation in overall mitochondrial protein synthesis in cell populations poses analytic challenges. Here, we adapted mitochondrial-specific fluorescent noncanonical amino acid tagging (FUNCAT) for use with fluorescence-activated cell sorting (FACS) and developed mito-FUNCAT-FACS. The click chemistry-compatible methionine analog L-homopropargylglycine (HPG) enabled the metabolic labeling of newly synthesized proteins. In the presence of cytosolic translation inhibitors, HPG was selectively incorporated into mitochondrial nascent proteins and conjugated to fluorophores via the click reaction (mito-FUNCAT). The application of in situ mito-FUNCAT to flow cytometry allowed us to separate changes in net mitochondrial translation activity from those of the organelle mass and detect variations in mitochondrial translation in cancer cells. Our approach provides a useful methodology for examining mitochondrial protein synthesis in individual cells.

As the prevalence of Long COVID increases, there is a critical need for a comprehensive assessment of disability. Our aims are to (1) characterise disability experiences among people living with Long COVID in Canada, UK, USA and Ireland; and (2) develop a patient-reported outcome measure to assess the presence, severity and episodic nature of disability with Long COVID.

In phase 1, we will conduct semistructured interviews with adults living with Long COVID to explore experiences of disability (dimensions, uncertainty, trajectories, influencing contextual factors) and establish an episodic disability (ED) framework in the context of Long COVID (n~10 each country). Using the conceptual framework, we will establish the Long COVID Episodic Disability Questionnaire (EDQ). In phase 2, we will examine the validity (construct, structural) and reliability (internal consistency, test-retest) of the EDQ for use in Long COVID. We will electronically administer the EDQ and four health status criterion measures with ain open access peer-reviewed journals and presentations.

This study was approved by the University of Toronto Research Ethics Board. Knowledge translation will occur with community collaborators in the form of presentations and publications in open access peer-reviewed journals and presentations.

To study the association between polypharmacy and the risk of hospitalisation and death in cases of COVID-19 in the population over the age of 65.

Population-based cohort study.

Quebec Integrated Chronic Disease Surveillance System, composed of five medico-administrative databases, in the province of Quebec, Canada.

32 476 COVID-19 cases aged over 65 whose diagnosis was made between 23 February 2020 and 15 March 2021, and who were covered by the public drug insurance plan (thus excluding those living in long-term care). We counted the number of different medications they claimed between 1 April 2019 and 31 March 2020.

Robust Poisson regression was used to calculate relative risk of hospitalisation and death associated with the use of multiple medications, adjusting for age, sex, chronic conditions, material and social deprivation and living environment.

Of the 32 476 COVID-19 cases included, 10 350 (32%) were hospitalised and 4146 (13%) died. Compared with 0-4 medications, polypharmacy exposure was associated with increased hospitalisations, with relative risks ranging from 1.11 (95% CI 1.04 to 1.19) for those using 5-9 medications to 1.62 (95% CI 1.51 to 1.75) for those using 20+. Similarly, the risk of death increased with the number of medications, from 1.13 (95% CI 0.99 to 1.30) for those using (5-9 medications to 1.97 (95% CI 1.70 to 2.27) (20+). Increased risk was mainly observed in younger groups.

Polypharmacy was significantly associated with the risk of hospitalisations and deaths related to COVID-19 in this cohort of older adults. Polypharmacy may represent a marker of vulnerability, especially for younger groups of older adults.

Polypharmacy was significantly associated with the risk of hospitalisations and deaths related to COVID-19 in this cohort of older adults. Polypharmacy may represent a marker of vulnerability, especially for younger groups of older adults.